MiR-34a／Bcl—2凋亡通路在年龄相关性聋小鼠模型中的作用  

Role of MiR-34a/Bcl-2 apoptotic pathway in age-related hearing loss of mouse model

作　　者：黄秋红[1] 陈玲[1] 郑亿庆[1] 熊浩[1] 杨海弟[1] 

机构地区：[1]中山大学孙逸仙纪念医院耳鼻喉-头颈外科中山大学听力及言语研究所,广州510120

出　　处：《中华老年医学杂志》2015年第9期1007-1010,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金青年基金（81400456）;广东省医学科研基金（B2014135）

摘　　要：目的探讨MiR-34a／Bcl-2凋亡通路在老年性聋发病机制中的可能作用。方法采用C57BL／6年龄相关性聋小鼠模型，4周龄小鼠和12月龄小鼠为研究对象，采用听性脑干诱发电位检查（ABR）进行听力测试，并检测听皮层神经元凋亡情况，采用聚合酶链反应（PCR）及免疫印迹分析（Western Blot）检测miR-34a／Bcl-2通路在年龄相关性聋小鼠听皮层的表达情况，并检测经典凋亡通路Caspase3的活化情况。结果ABR结果显示12月龄小鼠在频率为4kHz、8kHz、16kHz、32kHz的阈值分别为（80．0±2．5）dBHL、（74．0±3．5）dBHL、（86．0±4．6）dBHL、（87．0±6．6）dBHL，高于4周龄小鼠的（32．0±4．5）dBHL、（51．0±1．2）dBHL、（51．0±3．5）dBHL、（56．0±1．5）dBHL（均P〈0．05）。12月龄小鼠听皮层神经元数量减少，凋亡神经元增多，miR-34a的表达升高（t=6．02，P=0．001），Bcl-2的表达下降（t=7．12，P=0．032），Bax的表达升高（t=6．51，P=0．012），Caspase-3表达升高，4周龄小鼠与12月龄小鼠比较，差异有统计学意义（P=0．023）。结论MiR-34a／Bcl-2介导的凋亡通路可能是年龄相关性聋发病的机制之一。Objective To explore the possible mechanism of miR-34a/Bcl-2 apoptotic pathway in the mouse model of age-related hearing loss. Methods A C57BL/6 mouse model of age-related hearing loss was conducted, and 4-week-old and 12-month-old mice were considered as the objects. The auditory brainstem response （ABR） was used to test the hearing function. The TdT-mediated dUTP nick end labeling （TUNEL） was used to observe the apoptosis of neuron in auditory cortex. The mRNA and protein levels of miR-34a, Bcl-2 and caspase 3 were detected by real-time PCR and Western bloting, respectively. Results The ABR showed that the hearing threshold level at 4, 8, 16, 32 kHz were higher in 12-month-old mice than in 4-week-old mice [（80.0±2.5） dBHL vs. （32.0 ±4.5） dBHL, （74.0±3.5） dBHL w （51.0±1.2） dBHL, （86.0±4.6） dBHL vs. （51.0±3.5） dBHL, （87.0±6.6） dBHL w （56.0±1.5） dBHL, all P〈0.05]. Compared with 4-week-old mice, the total number of neurons in auditory cortex was decreased, the number of apoptosis neurons was increased, the expressions of miR 34a （ t=6.02, P= 0.001）, Bax （ t= 6.51, P= 0.012） and Caspase- 3 （P=0. 023） rised, and the expression of Bcl 2 （t=7. 12, P=0. 032） declined in 12 month-old mice. Conclusions The activation of miR-34a/Bcl-2 apoptotic pathway may be one of the mechanisms of age-related hearing loss.

关 键 词：老年性聋 细胞凋亡 

分 类 号：R764.43[医药卫生—耳鼻咽喉科] R-332[医药卫生—临床医学]